Pharmacologic Treatment Augmentation in Chronic Depression — Ket+CBASP  

Major Depressive Disorder Clinical Trial

Official title: Pharmacologic Treatment Augmentation in Chronic Depression "Randomized, Controlled, Double Blinded, Phase II Study"

Status Not yet recruiting

Clinical Trial Summary

To enroll in this clinical trial, prospective participants must meet stringent criteria. The participants need to fall within the age range of 18 to 64 and exhibit chronic depression at therapy resistance stage 2. This stage signifies that the participants have undergone unsuccessful treatment with at least two different antidepressants, despite adequate dosage and duration. Moreover, the participants should have engaged in at least 12 sessions of psychotherapy without experiencing significant relief from depressive symptoms. Additionally, participants must demonstrate the cognitive capacity to provide informed consent.

Upon expressing interest in the study and consenting to participate, individuals undergo a thorough screening process. This screening encompasses a comprehensive clinical interview to assess medical and psychiatric history, as well as various medical tests. These tests include physical examinations, blood draws (which may include pregnancy tests for female participants), and electrocardiograms (ECGs) to evaluate heart function. Following the screening, participants are randomly assigned to one of three different treatment groups (Ketamine +TAU; Ketamine+CBASP, Placebo+CBASP).

The study protocol involves a combination of psychotherapeutic treatment and either ketamine infusions or placebo. Throughout the study period, participants are subject to regular data collection, including psychological assessments, blood samples, and magnetic resonance imaging (MRI) scans. Participants' responses to treatment, as well as any changes in symptoms or side effects, are closely monitored.

After completing the study, participants are offered follow-up therapy as part of standard care. MRI scans are conducted to examine changes in brain activity associated with treatment response and depressive symptomatology, particularly focusing on alterations in neural circuitry and thought processes. Additionally, participants are encouraged to report any changes in medication regimen or other treatments received during the study period.

Clinical Trial Description

To participate in this clinical trial, one must have reached the age of 18 at the time of enrollment and not have exceeded the age of 64. Additionally, the pilot study is designed for patients with chronic depression who are in therapy resistance stage 2. Therapy resistance stage 2 means that one has taken at least 2 antidepressants from two different classes in sufficient dosage over a sufficient period of time without experiencing significant and sustainable improvement in depressive symptoms. Furthermore, one should have received at least 12 sessions of psychotherapy (psychoanalysis, psychodynamic psychotherapy, or cognitive behavioral therapy) without significant and sustainable improvement in depressive symptoms. Also, one must have the capacity to consent.

Those interested in participating in this study must have provided written consent to participate. A screening takes place to check the criteria for study participation using a clinical interview. The clinical interview collects information about current and previous physical and mental symptoms or diagnoses and treatments and lasts approximately 100 minutes. Additionally, a physical examination, a blood draw of approximately 20 ml, and an electrocardiogram (ECG) to determine heart activity are performed.

If one meets the inclusion criteria and no exclusion criteria are present, one can participate in the study and will be randomly assigned to one of the three treatment groups (Ketamine+TAU; Ketamine+CBASP, Placebo+CBASP). Participants are being told what type of psychotherapy the participant will receive. If one is assigned to one of the CBASP groups, neither the participant nor the treatment team will be informed whether the participant is receiving ketamine or placebo.

Once the group assignment is made, further data is collected in the first study week. In week 2, the psychotherapeutic treatment begins with a two-week introductory phase. Psychotherapy includes two individual sessions per week as well as group therapies. At the end of the introductory phase, further data collection takes place.

In week 3, additional data is collected, and a blood draw is performed to repeat the pregnancy test. Subsequently (weeks 4-6), one is treated with an infusion twice a week for three weeks (ketamine or placebo). The infusions within a week are spaced 2-3 days apart and each lasts approximately 40 minutes. Psychotherapy continues during these three weeks. After completing the combination treatment of study medication/placebo and psychotherapy, further data is collected, and psychotherapy continues for another 6 weeks (weeks 7-12). After that, the treatment as part of the study is completed.

To optimize treatment success and prevent relapses, an appropriate follow-up therapy is planned and initiated in consultation with the study therapist, depending on the individual development during the study therapy. Three months after completing the study therapy, the final data collection is carried out. Throughout the entire study, a total of 9 blood draws are performed.

Psychotherapy, administration of study medication/placebo, and data collection are carried out at the study site. Existing medication may continue to be taken during the study and will be optimized as needed. If medication with benzodiazepines is prescribed, it cannot be taken on the day before the infusion or on the day of the infusion.

The first blood draw and urine sample are used to get an impression of one's overall health status and thus assess whether participation in the study is possible or permissible according to the inclusion and exclusion criteria. In addition, a drug screening is performed on the urine sample to exclude acute substance abuse (alcohol, drugs), and a pregnancy test is performed based on the blood sample.

In the event of discontinuation of the study, follow-up treatment will be offered within the standard therapy for depressive disorders.

Additional medications (including over-the-counter ones) of which the investigator is not yet aware may only be taken in emergencies after consulting the investigator. If one is being treated by other doctors, the other doctors must be informed about participation in the clinical trial. The investigator must also be informed about any medical treatment received from another doctor during the clinical trial. One will receive a study ID card, which should always be carried for emergencies.

The fMRI examination in weeks 3 and 12 is performed to assess changes in brain activity during treatment and in relation to changes in depressive symptoms. Additionally, the relationship between mind wandering and brain activity in the presence of depressive illness is analyzed. ;

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

• NCT number: NCT06410599
• Study type: Interventional
• Source: University Hospital Tuebingen
• Contact: Martin Walter, Prof. Dr.
• Phone: +493641 9390101
• Email: martin.walter@med.uni-jena.de
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 2024
• Completion date: July 2026